Drug Interactions between dasatinib and troleandomycin

Do not consume grapefruit or grapefruit juice during treatment with dasatinib. Grapefruit juice can significantly increase the blood levels and effects of dasatinib, which may result in excessive slowing of heart rate or other conduction disturbances and it may affect your bone marrow function, resulting in low numbers of different types of blood cells. You may be more likely to develop anemia, bleeding problems, or infections due to low blood cell counts. Talk to your doctor if you have any questions or concerns. You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, heart palpitations, paleness, fatigue, unusual bruising or bleeding, fever, chills, diarrhea, sore throat, muscle aches, blood in phlegm, weight loss, pain or burning during urination, red or inflamed skin, or body sores during treatment with dasatinib. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Troleandomycin is primarily excreted by the liver and may accumulate in patients with impaired hepatic function. In addition, the use of troleandomycin has been associated with an allergic type of cholestatic hepatitis, particularly in patients receiving the drug for more than 2 weeks or given repeated courses. Therapy with troleandomycin should be administered cautiously in patients with liver and/or biliary disease. Liver function tests should be monitored during prolonged or repeated courses of therapy, and the drug discontinued if abnormalities develop.

Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.

Troleandomycin is primarily excreted by the liver and may accumulate in patients with impaired hepatic function. In addition, the use of troleandomycin has been associated with an allergic type of cholestatic hepatitis, particularly in patients receiving the drug for more than 2 weeks or given repeated courses. Therapy with troleandomycin should be administered cautiously in patients with liver and/or biliary disease. Liver function tests should be monitored during prolonged or repeated courses of therapy, and the drug discontinued if abnormalities develop.

Thrombocytopenia, aplastic anemia, agranulocytosis and neutropenia occur with BCR-ABL tyrosine kinase inhibitors. Therapy with these drugs should be administered cautiously in patients with preexisting bone marrow suppression. A complete blood count should be performed every 1-2 weeks for the first month of therapy and then monthly thereafter, or as clinically indicated. To manage myelosuppression, withhold, reduce dose, or discontinue therapy as necessary.

Cardiovascular events, including arterial vascular occlusive events, peripheral arterial occlusive events and ischemic cerebrovascular events have been reported in patients receiving tyrosine kinase inhibitors. If acute signs or symptoms of cardiovascular events occur, patients should seek immediate medical attention. The cardiovascular status and risk factors of patients should be evaluated prior to therapy and cardiovascular monitoring and management should take place during treatment.

Fluid retention occurs with BCR-ABL tyrosine kinase inhibitors therapy and may manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Caution should be taken when using these drugs in patients with preexisting fluid retention or congestive heart failure. Monitor and manage patients using standards of care. Interrupt, reduce dose or discontinue therapy as necessary.

Fluid retention occurs with BCR-ABL tyrosine kinase inhibitors therapy and may manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Caution should be taken when using these drugs in patients with preexisting fluid retention or congestive heart failure. Monitor and manage patients using standards of care. Interrupt, reduce dose or discontinue therapy as necessary.

Dasatinib has shown to prolong QT interval in a concentration-dependent manner. Caution should be exercised specially in patients with congenital long QT syndrome, patients with hypokalemia, hypomagnesemia, or with history of arrhythmias and on antiarrhythmic medication. Hypokalemia or hypomagnesemia should be corrected before starting treatment. Patients at risk should be monitored with an EKG before treatment and periodically as clinically indicated. Dose adjustments might be needed.

Caution is advised when administering dasatinib to patients with hepatic impairment. Monitoring is recommended and dose adjustment might be necessary.

Dasatinib has shown to prolong QT interval in a concentration-dependent manner. Caution should be exercised specially in patients with congenital long QT syndrome, patients with hypokalemia, hypomagnesemia, or with history of arrhythmias and on antiarrhythmic medication. Hypokalemia or hypomagnesemia should be corrected before starting treatment. Patients at risk should be monitored with an EKG before treatment and periodically as clinically indicated. Dose adjustments might be needed.

Dasatinib has shown to prolong QT interval in a concentration-dependent manner. Caution should be exercised specially in patients with congenital long QT syndrome, patients with hypokalemia, hypomagnesemia, or with history of arrhythmias and on antiarrhythmic medication. Hypokalemia or hypomagnesemia should be corrected before starting treatment. Patients at risk should be monitored with an EKG before treatment and periodically as clinically indicated. Dose adjustments might be needed.

Fluid retention occurs with BCR-ABL tyrosine kinase inhibitors therapy and may manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Caution should be taken when using these drugs in patients with preexisting fluid retention or congestive heart failure. Monitor and manage patients using standards of care. Interrupt, reduce dose or discontinue therapy as necessary.

Dasatinib can increase the risk of developing pulmonary arterial hypertension (PAH) which may occur any time after treatment initiation, including after more than 1 year of treatment. Manifestations may include dyspnea, fatigue, hypoxia, and fluid retention. PAH may be reversible with treatment discontinuation. Caution should be exercised in patients with underlying cardiopulmonary disease. If PAH develops, treatment should be discontinued.